Abstract
Exosomes are nano‐sized vesicles that are involved in various biological processes including cell differentiation, proliferation, signaling, and intercellular communication. Urinary exosomes were isolated from a cohort of hereditary α‐tryptasemia (HαT) patients and from healthy volunteers. There was a greater number of exosomes isolated from the urine in the HαT group compared to the control volunteers. Here, we investigated the differences in both lipid classes and lipid species within urinary exosomes of the two groups. Lipids were extracted from urinary exosomes and subjected to liquid chromatography mass spectrometry using a targeted approach. Various molecular species of glycerophospholipids, glycerolipids, and sterols were significantly reduced in HαT patients. Out of a possible 1127 lipids, 521 lipid species were detected, and relative quantities were calculated. Sixty‐four lipids were significantly reduced in urinary exosomes of HαT patients compared to controls. All significantly reduced sphingolipids and most of the phospholipids were saturated or mono‐unsaturated lipids. These results suggest exosome secretion is augmented in HαT patients and the lipids within these exosomes may be involved in various biological processes. The unique lipid composition of urinary exosomes from HαT patients will contribute to our understanding of the biochemistry of this disease.
Highlights
Hereditary α‐tryptasemia (HαT) is characterized by dominant inheritance of multiple copies of α‐tryptase‐encoding sequence for TPSAB1 leading to basal serum tryptase (BST) elevations.[1,2,3,4]
We focused on the isolation of exosomes from the urine of HαT patients and healthy volunteers and the analysis of exosome lipids in this study
Since exosomes secretion and urine production may vary within a 24‐hour cycle, all urine samples were collected between 9‐11AM All patient and donor information were coded and not revealed until the data were analyzed at the end of the study
Summary
Hereditary α‐tryptasemia (HαT) is a recently identified, genetic disorder associated with elevated basal serum tryptase (BST) and multisystem, clinical phenotypes.[1,2,3,4] HαT is characterized by dominant inheritance of multiple copies of α‐tryptase‐encoding sequence for TPSAB1 leading to BST elevations.[1,2,3,4] The incidence of this genetic disorder is the subject of ongoing investigations. Exosomes are nano‐sized vesicles derived from the endosomal network that have been shown to play an important role in various biological processes including intercellular communication,[12,13,14,15] cell differentiation,[16,17] proliferation,[18,19] and intracellular signaling.[20] The physiological and pathophysiological roles of exosomes are mediated by the packaged material that they carry which include mRNAs, miRNAs, lipids, and various types of proteins.[21] Exosomes are secreted by most cell types and can be found in biological fluids including urine, blood, cerebrospinal fluid, and saliva.[22,23] Exosomes are secreted into the extracellular milieu by exocytosis from multivesicular bodies that originate from late endosomes.
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